Dielectric permittivity of microbial suspensions at radio frequencies: a novel method for the real-time estimation of microbial biomass

Harris, Christine; Todd, Robert W.; Bungard, Stephen J.; Lovitt, Robert W.; Morris, Jonathan; Kell, Douglas B.

doi:10.1016/0141-0229(87)90075-5

Cited by 242 publications

(146 citation statements)

References 25 publications

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“…[33][34][35][36] The permittivity of a cell suspension can be easily measured because a characteristic fall in permittivity, the b-dispersion (Figure 1), occurs with increasing frequency. The b-dispersion is caused by the polarization of cell membranes.…”

Section: Theoretical Backgroundmentioning

confidence: 99%

“…6 In fact, its most commonly used definition is rather operational and might in some case also include necromass. 7 Consequently, many different methods are available for biomass determination. On the one hand, classical on-line biomass measurement techniques like the calculation of the oxygen uptake rate (OUR) or the CO 2 evolution rate (CER) give indirect information on the biomass content.…”

Section: Introductionmentioning

confidence: 99%

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Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Ansorge

Esteban

Schmid

2009

Biotechnology Progress

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Lab and pilot scale batch cultivations of a CHO K1/dhfr À host cell line were conducted to evaluate on-line multifrequency permittivity measurements as a process monitoring tool. The b-dispersion parameters such as the characteristic frequency (f C ) and the permittivity increment (De max ) were calculated on-line from the permittivity spectra. The dual-frequency permittivity signal correlated well with the off-line measured biovolume and the viable cell density. A significant drop in permittivity was monitored at the transition from exponential growth to a phase with reduced growth rate. Although not reflected in off-line biovolume measurements, this decrease coincided with a drop in OUR and was probably caused by the depletion of glutamine and a metabolic shift occurring at the same time. Sudden changes in cell density, cell size, viability, capacitance per membrane area (C M ), and effects caused by medium conductivity (r m ) could be excluded as reasons for the decrease in permittivity. After analysis of the process data, a drop in f C as a result of a fall in intracellular conductivity (r i ) was identified as responsible for the observed changes in the dual-frequency permittivity signal. It is hypothesized that the b-dispersion parameter f C is indicative of changes in nutrient availability that have an impact on intracellular conductivity r i . On-line permittivity measurements consequently not only reflect the biovolume but also the physiological state of mammalian cell cultures. These findings should pave the way for a better understanding of the intracellular state of cells and render permittivity measurements an important tool in process development and control.

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Section: Theoretical Backgroundmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Ansorge

Esteban

Schmid

2009

Biotechnology Progress

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“…The underlying theory on the dielectric properties of biological cells has been extensively described elsewhere (Kell and Harris 1985;Harris et al 1987;Pethig and Kell 1987;Markx and Davey 1999). In summary, the permittivity of a cell suspension can be easily measured because a characteristic fall in its value, the b-dispersion, occurs with increasing frequency.…”

Section: Permittivity Measurements With the Fogale Biomass Systemmentioning

confidence: 99%

On-line monitoring of responses to nutrient feed additions by multi-frequency permittivity measurements in fed-batch cultivations of CHO cells

2010

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Changes in the nutrient availability of mammalian cell cultures are reflected in the bdispersion parameter characteristic frequency (f C ) and the on-line dual frequency permittivity signal. Multifrequency permittivity measurements were therefore evaluated in fed-batch cultivations of two different CHO cell lines. Similar responses to nutrient depletions and discontinuous feed additions were monitored in different cultivation phases and experimental setups. Sudden increases in permittivity and f C occurred when feed additions were conducted. A constant or declining permittivity value in combination with a decrease in f C indicated nutrient limitations. f C correlated well with changes in oxygen uptake rate when cell diameter remained constant, indicating that metabolic activity is reflected in the value of f C . When significant cell size changes occurred during the cultivations, the analysis of the b-dispersion parameters was rendered complex. For the application of our findings in other systems it will be hence required to conduct additional off-line measurements. Based on these results, it is hypothesized that multi-frequency permittivity measurements can give information on the intracellular or physiological state in fed-batch mode. Similar observations were made when using different cell lines and feeding strategies, indicating that the findings are transferable to other cell lines and systems. The results should lead to an improved understanding of routine fed-batch processes. Additional studies are, however, required to explore how these observations can be used for fed-batch process development and optimization.

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“…7 An important potential application of dielectric measurements on engineered tissues is the on-line and continuous measurement of the cell concentration and its distribution within a tissue construct. 8,9 An example of the on-line measurement of cell concentration in a tissue construct is shown in Figure 1.…”

Section: Characterization Of Cells and Tissues Using Electrical Technmentioning

confidence: 99%

The use of electric fields in tissue engineering

Markx¹

2008

Organogenesis

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Dielectric permittivity of microbial suspensions at radio frequencies: a novel method for the real-time estimation of microbial biomass

Cited by 242 publications

References 25 publications

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

Multifrequency permittivity measurements enable on‐line monitoring of changes in intracellular conductivity due to nutrient limitations during batch cultivations of CHO cells

On-line monitoring of responses to nutrient feed additions by multi-frequency permittivity measurements in fed-batch cultivations of CHO cells

The use of electric fields in tissue engineering

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